It is known that the acute loss of more than 60% of liver function is a serious risk to survival. It is also known that patients with chronic liver insufficiency may have periods when a metabolic stress such as surgery or an infection places them in liver failure. The liver serves to remove impurities from the blood and either recycles them to useful compounds, or converts them to harmless waste products which are excreted by the kidneys. Without a properly functioning liver, the body is unable to maintain its normal metabolic balance, and many organs cease to function because of the build-up of toxins or because the liver is no longer synthesizing important nutrients. The functions of the liver are not completely known, but are such that simple removal of toxins from the blood by hemodialysis or hemoperfusion does not alleviate the patient's condition. Removal of toxins by these methods may improve one or more aspects of the patient's condition such as acid-base balance or mental status, but the overall condition is unaffected, and mortality is not improved.
Even though the liver is the only organ capable of regeneration, severe liver failure does not provide the optimum metabolic circumstances for such regeneration to take place. Faced with a rapidly deteriorating patient, the only successful treatment to date has been the removal of the failing liver and transplantation with a donor liver. There are, however, several major concerns with liver transplantation including the procurement of a matching organ within a useful time frame, the transport of the organ to the patient, major surgery which carries a 10-20% mortality, the continuing danger of rejection of the transplanted organ, and the expenses involved in the operation and subsequent medical care of the patient.
In view of the foregoing concerns, potential uses for a liver support system include supporting a patient until recovery from a metabolic stress, sustaining a liver transplant candidate until a suitable organ is available, and supporting a patient after transplantation until the grafted liver is functioning adequately and can fully sustain the patient. The solution to the problem is a metabolically-active liver assist device, i.e., one containing functioning liver cells. Implementation of such a device raises several problems which have not previously been encountered in extracorporeal blood therapies. These problems include inter alia:
The need for a continuous oxygen supply to maintain cell viability; PA1 The need to maintain a positive pressure gradient from the ICS to the ECS to prevent cells from migrating into the ICS in the event of a fiber rupture; PA1 The need to perfuse the ECS in order to reduce the concentration of clotting factors, thus reducing the likelihood of blood clotting in the cartridge; PA1 The need to monitor the fluid in the ECS to assess the continuing viability of cells in the ECS; PA1 The need to return fluid from the ECS to the patient's blood stream in order to supply proteins which are secreted by the cells; and PA1 The need to temporarily support the metabolic requirements of a cartridge while the need for further treatment is evaluated.